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Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.

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posted on 22.11.2019, 17:30 by Suzanne A Eccles, Eric O. Aboagye, Simak Ali, Annie S. Anderson, Jo Armes, Fedor Berditchevski, Jeremy P. Blaydes, Keith Brennan, Nicola J. Brown, Helen E. Bryant, Nigel J. Bundred, Joy M. Burchell, Anna M. Campbell, Jason S. Carroll, Robert B. Clarke, Charlotte E. Coles, Gary Jr Cook, Angela Cox, Nicola J. Curtin, Lodewijk V V. Dekker, Isabel Dos Santos Silva, Stephen W. Duffy, Douglas F. Easton, Diana M. Eccles, Dylan R. Edwards, Joanne Edwards, D Gareth Evans, Deborah F. Fenlon, James M. Flanagan, Claire Foster, William M. Gallagher, Montserrat Garcia-Closas, Julia MW Gee, Andy J. Gescher, Vicky Goh, Ashley M. Groves, Amanda J. Harvey, Michelle Harvie, Bryan T. Hennessy, Stephen Hiscox, Ingunn Holen, Sacha J. Howell, Anthony Howell, Gill Hubbard, Nick Hulbert-Williams, Myra S. Hunter, Bharat Jasani, Louise J. Jones, Timothy J. Key, Cliona C. Kirwan, Anthony Kong, Ian H. Kunkler, Simon P. Langdon, Martin O. Leach, David J. Mann, John F. Marshall, Lesley A. Martin, Stewart G. Martin, Jennifer E. Macdougall, David W. Miles, William R. Miller, Joanna R. Morris, Sue M. Moss, Paul Mullan, Rachel Natrajan, James PB O'Connor, Rosemary O'Connor, Carlo Palmieri, Paul DP Pharoah, Emad A. Rakha, Elizabeth Reed, Simon P. Robinson, Erik Sahai, John M. Saxton, Peter Schmid, Matthew J. Smalley, Valerie Speirs, Robert Stein, John Stingl, Charles H. Streuli, Andrew NJ Tutt, Galina Velikova, Rosemary A. Walker, Christine J. Watson, Kaye J. Williams, Leonie S. Young, Alastair M. Thompson

INTRODUCTION: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.

METHODS: More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.

RESULTS: The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.

CONCLUSIONS: With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

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AfatinibATM proteinbiological markerBRCA1 proteinBRCA2 proteincheckpoint kinase 2denosumabeverolimusfenretinideganetespibgoserelinlapatiniblasofoxifeneletrozoleluminespibmetforminneratinibpaclitaxelpertuzumabphosphatidylinositol 35 trisphosphate 3 phosphataseprotein kinase LKB1protein p53raloxifeneresveratrolsaracatinibtamoxifentrastuzumabuvomorulinabdominal obesityadvanced canceralcohol consumptionalleleangiogenesisarticlebehavior changebioinformaticsbody compositionbody weightbone metastasisbreast cancerbreast developmentbreast metastasisbreast reconstructioncaloric restrictioncancer adjuvant therapycancer epidemiologycancer geneticscancer hormone therapycancer immunotherapycancer prognosiscancer riskcancer survivalcancer susceptibilitycell deathcell lineagecell polaritychemosensitivitycirculating tumor cellclinical decision makingcognitive therapycost effectiveness analysiscytologydistant metastasisDNA damagedrug efficacyepigeneticsepithelial mesenchymal transitionexercisefat intakefine needle aspiration biopsygene expressiongenetic associationgenetic predispositiongenetic screeninggenetic susceptibilitygenetic variabilitygenotypehormonal therapyhumanin vitro studyin vivo studylifestyle modificationlongevitylow drug doselymphangiogenesismalignant transformationmastectomymedical researchmeta analysis (topic)micrometastasismolecularly targeted therapymonotherapynonhumannuclear magnetic resonance imagingpatient satisfactionpersonalized medicinephase 3 clinical trial (topic)physical activitypositron emission tomographypsychological well beingquality of liferadiofrequency ablationradiosensitivityrandomized controlled trial (topic)signal transductionsingle nucleotide polymorphismsmokingsocial marketingstereotactic body radiation therapyterminal caretranslational researchtumor microenvironmenttumor xenograft.

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The original article is available at www.biomedcentral.com

Published Citation

Eccles SA, Aboagye EO, Ali S, Anderson AS, Armes J, Berditchevski F, Blaydes JP, Brennan K, Brown NJ, Bryant HE, Bundred NJ, Burchell JM, Campbell AM, Carroll JS, Clarke RB, Coles CE, Cook GJ, Cox A, Curtin NJ, Dekker LVV, dos Santos Silva I, Duffy SW, Easton DF, Eccles DM, Edwards DR, Edwards J, Evans DG, Fenlon DF, Flanagan JM, Foster C, Gallagher WM, Garcia-Closas M, Gee JMW, Gescher AJ, Goh V, Groves AM, Harvey AJ, Harvie M, Hennessy BT, Hiscox S, Holen I, Howell SJ, Howell A,Hubbard G, Hulbert-Williams N, Hunter MS, Jasani B, Jones LJ, Key TJ, Kirwan CC, Kong A, Kunkler IH, Langdon SP, Leach MO, Mann DJ, Marshall JF, Martin LA, Martin SG, Macdougall JE, Miles DW, Miller MR, Morris JR, Moss SM, Mullan P, Natrajan R, O’Connor JPB, O’Connor R, Palmieri C, Pharoah PDP, Rakha EA, Reed E, Robinson SP, Sahai E, Saxton JM, Schmid P, Smalley MJ, Speirs V, Stein R, Stingl J, Streuli CH, Tutt ANJ, Velikova G, Walker RA, Watson CJ, Williams KJ, Young LS, Thompson AM. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research. 2013;15(5):R92.

Publication Date

01/10/2013

PubMed ID

24286369

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Categories

Keywords

AfatinibATM proteinbiological markerBRCA1 proteinBRCA2 proteincheckpoint kinase 2denosumabeverolimusfenretinideganetespibgoserelinlapatiniblasofoxifeneletrozoleluminespibmetforminneratinibpaclitaxelpertuzumabphosphatidylinositol 35 trisphosphate 3 phosphataseprotein kinase LKB1protein p53raloxifeneresveratrolsaracatinibtamoxifentrastuzumabuvomorulinabdominal obesityadvanced canceralcohol consumptionalleleangiogenesisarticlebehavior changebioinformaticsbody compositionbody weightbone metastasisbreast cancerbreast developmentbreast metastasisbreast reconstructioncaloric restrictioncancer adjuvant therapycancer epidemiologycancer geneticscancer hormone therapycancer immunotherapycancer prognosiscancer riskcancer survivalcancer susceptibilitycell deathcell lineagecell polaritychemosensitivitycirculating tumor cellclinical decision makingcognitive therapycost effectiveness analysiscytologydistant metastasisDNA damagedrug efficacyepigeneticsepithelial mesenchymal transitionexercisefat intakefine needle aspiration biopsygene expressiongenetic associationgenetic predispositiongenetic screeninggenetic susceptibilitygenetic variabilitygenotypehormonal therapyhumanin vitro studyin vivo studylifestyle modificationlongevitylow drug doselymphangiogenesismalignant transformationmastectomymedical researchmeta analysis (topic)micrometastasismolecularly targeted therapymonotherapynonhumannuclear magnetic resonance imagingpatient satisfactionpersonalized medicinephase 3 clinical trial (topic)physical activitypositron emission tomographypsychological well beingquality of liferadiofrequency ablationradiosensitivityrandomized controlled trial (topic)signal transductionsingle nucleotide polymorphismsmokingsocial marketingstereotactic body radiation therapyterminal caretranslational researchtumor microenvironmenttumor xenograft.

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